Available online at www.sciencedirect.
com
ScienceDirect
Hidden hypotheses in ‘hypothesis-free’ genome-wide epigenetic
associations
Edward D Barker1, Susanna Roberts1 and Esther Walton2
The recent interest in epigenetics within mental health
research, from a developmental perspective, stems from the
potential of DNA methylation to index both exposure to
adversity and vulnerability for mental health problems.
Genome-wide technology has facilitated epigenome-wide
association studies (EWAS), permitting ‘hypothesis-free’
examinations in relation to adversity and/or mental health
problems. In EWAS, rather than focusing on a priori established
candidate genes, the genome is screened for DNA methylation,
thereby enabling a more comprehensive representation of
variation associated with complex disease. Despite their
‘hypothesis-free’ label, however, results of EWAS are in fact
conditional on several a priori hypotheses, dictated by the
design of EWAS platforms as well as assumptions regarding
the relevance of the biological tissue for mental health
phenotypes. In this short report, we review three hidden
hypotheses — and provide recommendations — that
combined will be useful in designing and interpreting EWAS
projects.
Addresses
1
Department of Psychology, Institute of Psychiatry, Psychology and
Neuroscience, King’s College London, UK
2
Medical Research Council Integrative Epidemiology Unit and Bristol
Medical School, Population Health Sciences, University of Bristol, UK
Corresponding author: Barker, Edward D (ted.barker@kcl.ac.uk)
Current Opinion in Psychology 2019, 27:13–17
This review comes from a themed issue on Genetics
Edited by Brian Boutwell and Michael A White
https://doi.org/10.1016/j.copsyc.2018.07.009
2352-250X/ã 2018 The Authors. Published by Elsevier Ltd. This is an
open access article under the CC BY-NC-ND license (http://creative-
commons.org/licenses/by-nc-nd/4.0/).
Understanding the biological mechanisms by which early
psychosocial adversity associates with long-term mental
health problems may have the potential to facilitate the
development of effective screening, intervention strate-
gies and health policy decisions [1]. Recent research has
focused on the degree to which adversity disrupt gene
regulation through epigenetic processes, thereby provid-
ing a mechanism by which the environment can have
lasting effects on measurable mental health phenotypes
[2]. High profile studies suggest that epigenetic changes
associated with early adversities [3,4] and even lifestyle
www.sciencedirect.com
choices [5] can be observed across the life span, and that
these long-term epigenetic modifications are associated
with risk for a range of health outcomes [6]. These studies
have generally focused on DNA methylation (DNAm) for
two reasons: it is currently the best understood epigenetic
mechanism and array-based technologies are readily
available, which provides coverage of hundreds of thou-
sands of methylation sites across the genome [7]. This
combination of basic science and genome-wide technol-
ogy has facilitated numerous epigenome-wide association
studies (EWAS), permitting ‘hypothesis-free’ examina-
tions in relation to adversity and/or mental health
problems.
The logic underlying EWAS is comparable to genome-
wide association studies (GWAS [8]). Rather than focus-
ing on DNAm in proximity to candidate genes, the
genome is screened for DNAm, thus enabling a more
comprehensive representation of variation associated
with complex disease. As with GWAS (e.g. [9,10]),
despite their ‘hypothesis-free’ label, results of EWAS
are in fact conditional on several a priori hypotheses,
dictated by the design of EWAS platforms as well as
assumptions regarding the relevance of the biological
tissue for the mental health phenotypes under investiga-
tion. In this short report, we review three hidden hypoth-
eses (see Figure 1) — and provide recommendations —
that combined will be useful in designing and interpret-
ing EWAS projects.
Hidden hypothesis 1: EWAS coverage is
sufficient for complex psychiatric problems
Array-based platforms have become widespread in psy-
chology research, largely due to their ease of use, rela-
tively high through-put, and well standardised and vali-
dated pipelines for processing, quality control, and
analysis techniques. In particular, the Illumina 450k
and EPIC arrays feature 480 000–850 000 probes targeting
nearly 99% of RefSeq genes, as well as a range of other
genomic categories, such as CpG islands, shores and
shelves, miRNA promoters and enhancers, where DNAm
can be influenced by and/or impact transcription in distal
genomic regions [11]. Compared with the Ilumina 450k,
the newer Illumina EPIC 850k array provides much
greater coverage of ENCODE and FANTOM5 enhan-
cers [12], and shows higher genetic influence underly-
ing DNAm probes [13]. Nevertheless, these microarrays
are limited in the number of sites they can assess, and thus
lack true genome-wide measurements [14].
Current Opinion in Psychology 2019, 27:13–17
14 Genetics
Figure 1
3
M covered
M relevant
M covered / relevant
Hidden hypotheses in epigenome-wide approaches. Note: (1) = Hypothesis 1: EWAS coverage is sufficient for complex psychiatric problems;
(2) = Hypothesis 2: peripheral tissue is meaningful for mental health problem(s); and (3) = Hypothesis 3: biology can be meaningful to phenotype of
interest.
Furthermore, during the design process of the 450k and
EPIC arrays, CpG sites were chosen as potentially bio-
logically informative based on consultation with a consor-
tium of DNA methylation experts [15]. Whilst the cover-
age of genes and CpG islands on these microarrays are
comprehensive, it does not represent a complete picture
of methylated cytosines across the genome. Selection
was, in part, based on data from a number of phenotypes
(some medical in nature such as cancer), and thus is not
specifically targeted to brain-based, stress-related com-
plex mental health phenotypes. This is an important
point: if a sizeable proportion of the CpG sites tested
are not relevant to the phenotype of interest, the likeli-
hood of detecting relevant results is reduced.
Hidden hypothesis 2: peripheral tissue is
meaningful for mental health problem(s)
The second hidden hypothesis relates to the tissue that is
used to quantify DNAm. The majority of mental health
research is based on DNAm profiles obtained from
peripheral tissues from living persons, such as blood
and saliva. When investigating outcomes such as conduct
Current Opinion in Psychology 2019, 27:13–17
2
Epithelial Blood
Current Opinion in Psychology
disorder or depression, however, the brain is often the
main tissue of interest when it comes to mechanistic
interpretations of results [16]. To this end, research
suggests that the correspondence of methylation profiles
from blood and saliva to the brain is in fact quite limited,
but can be higher with cross-tissue genetic influence
[13,17]. This presents a critical disadvantage if the inves-
tigator would like to use the peripheral tissue as a surro-
gate of the central nervous system (CNS; the brain).
One promising avenue is to establish DNAm as a bio-
marker for mental illness. A biomarker does not have to
be mechanistic (i.e. CNS surrogate). Indeed, blood-based
biomarkers have been used for diagnostics, predictive
risk, disease monitoring and/or treatment response in
cancer, cardiovascular and infectious disease [18,19].
However, even within a biomarker framework, the
assumption is often that distinct peripheral tissues are
interchangeable and equally suited for biomarker detec-
tion, when in fact it is highly probable that peripheral
tissues themselves correspond differently to environmen-
tal adversity and/or disease state [14]. For instance,
www.sciencedirect.com

biomarkers for mental health traits (e.g. depression) may
be more detected in blood than saliva, as blood is more
central to inflammatory processes related to stress and
disease [16].
Hidden hypothesis 3: biological relevance for
the phenotype of interest
The last hypothesis relates to the assumption that biology
can be informative to the phenotype itself. Focal pheno-
types (e.g. oppositional defiant disorder, anxiety) in men-
tal health research are often complex and multiply deter-
mined [20]. The lack of established robust biomarkers for
mental health problems (e.g. [19]) may suggest that some
of these traits might not strongly associate with detectable
biological processes. Furthermore, effect size associations
in EWASes are often very small suggesting that — while
significant — distinguishing the importance of DNAm in
the aetiology of the mental health phenotype may prove
difficult [21]. Perhaps unsurprisingly then, most EWAS
in mental health include some form of gene ontology
analysis, which queries the role of larger biological sys-
tems based on existing databases [22]. These analyses
result in general statements such as ‘neurodevelopment’
or the ‘immune system’ being involved in the aetiology of
a given phenotype. Whether these broad categories play
indeed a substantial role in the aetiology of the mental
health problem is often hard to determine given the post
hoc nature of the interpretation. Relatedly, many
EWASes have tried to infer downstream effects of
observed variation in DNAm such as differences in gene
expression. Many of these studies find very little in terms
of functional relationships, but a small number do report
downstream biological associations (e.g. [21]). In gen-
eral, it has proven difficult to pinpoint EWAS-related
biological relevance of observed DNAm changes, even
if they are in genes which seem ‘plausible’ based on
reported functionality and previous literature.
Recommendation for hidden hypothesis 1:
EWAS coverage
An alternative to using arrays with limited coverage is to
use next-generation sequencing-based approaches to
interrogate the whole methylome [21]. However, these
methodologies are high in cost and time intensive.
Despite the limitations described above, pragmatic and
strategic study design can maximise utility and interpre-
tation of results of the Illumina 450k and EPIC arrays. For
example, for researchers interested in targeting CpGs
likely to associate with ‘brain-based’ mental illnesses,
an a priori set of CpGs (e.g. a ‘systems approach’) could
be isolated from the array data, which could still span
thousands of loci. The suggestion is to prioritize CpGs
within biological systems that are known to associate with
variation in post-mortem brain samples [23] or even
structural or functioning brain imaging [24] if this is of
primary interest to the investigator.
www.sciencedirect.com
Hidden hypotheses Barker, Roberts and Walton 15
The second recommendation for optimising the use of
EWAS CpGs is to target those probes with underlying
genetic influence — methylation quantitative trait loci
(mQTLs). This approach may have the advantage that
cross-tissue concordance (e.g. blood, saliva, post-mortem
brain) appears higher for CpGs that show cross-tissue
genetic influence [13]. Another advantage of mQTLs is
that CpGs under considerable genetic influence are less
affected by confounds [11,13,25]. However, while
mQTLs are a worthwhile approach, it is a relatively
new area and at present, there is a small proportion of
methylation sites with consistently reported mQTLs
[11,13]. Furthermore, large-scale and detailed informa-
tion on tissue-specific mQTLs is still sparse.
Recommendation for hidden hypothesis 2:
peripheral tissue and phenotype
One strategy to maximise the interpretability of EWAS
projects is to examine DNAm as a biomarker for mental
health problems that have mechanistic underpinning in
tissues other than the brain, such as blood. A wide-range
of psychiatric disorders have been associated with
immune function as measured by peripheral inflamma-
tion [26]. Furthermore, there is good evidence from
animal studies, and increasing evidence in humans, that
peripheral inflammatory markers can affect brain areas
implicated in certain psychiatric disorders [27]. Conse-
quently, adversity-related immune processes and DNAm
may be well measured in blood samples (see [28]). For
biomarkers to be useful, they must be cost effective,
drawn from accessible tissue and predictive of future risk
[29]. Biomarkers for brain-based disorders (e.g. depres-
sion) have proven more difficult to establish [19]. Liu et al.
[30] performed an EWAS on blood tissues across 13 pop-
ulation-based cohorts and reported that a composite bio-
marker (consisting of 144 CpGs) discriminated drinkers
from non-drinkers. It was thus suggested that a blood-
based DNAm diagnostic test could be developed. It is
important to note, however, that in addition to methodo-
logical considerations [31], the Liu et al. study was cross-
sectional, thus it may prove difficult to use this specific
biomarker as a predictor of future alcohol use, as the
variation in DNAm may be the result of chronic drinking
(i.e. reverse causality [32]). Importantly, large-scale meta-
analyses based on new and growing consortia (e.g. PACE
[33]) are beginning to report consistent epigenetic
effects on traits such as schizophrenia or smoking behav-
iour (e.g. [34,35]) which suggests that we may begin to be
able to utilise this information to further optimize DNAm
biomarker approaches.
Recommendation for hidden hypothesis 3:
phenotype and biology
Several suggestions have been put forward to address the
complex nature of the biology that may underlie mental
health problems. Most notably, the Research Domain
Criteria (RDoC) initiative has proposed alternative
Current Opinion in Psychology 2019, 27:13–17
16 Genetics
approaches to study mental illness by integrating many
different levels of information including genetics, neu-
rocircuits and behaviour [36]. Methylation-based research
can be integrated into an RDoC perspective. Here,
researchers could employ a two-stage analysis, first inves-
tigating epigenetic effects on intermediate dimensions of
mental health and then, using the results as biomarkers to
query the more complex phenotypes. For, example, if
externalising difficulties (e.g. ADHD, aggression) are the
focal phenotype, rather than performing an EWAS
directly on the disorder(s), the researchers could instead,
as the first step, perform an EWAS on brain imaging
endophenotypes of the externalising phenotype (e.g.
[24]). In the second step, the results of the EWAS could
be used to create poly-epigenetic genetic biomarker score
(e.g. [28]) to be (potentially) associated with the disor-
der. This type of two stage of EWAS may examine the
epigenetic changes associated with antecedents of diag-
nosable mental health conditions, which would be could
be more useful as a risk biomarker than a biomarker of the
actual diagnosis.
Conclusion
The recent interest in epigenetics, from a developmental
perspective, stems from the potential of DNA methyla-
tion to index both exposure to adversity and vulnerability
for mental health problems [2]. To this end, there has
been substantial activity in examining EWASes of adver-
sity-related disorders, such as conduct disorder [37] and
psychosis [38]. Of interest, from these EWAS, DNAm in
genes that underlie stress response, neurotransmitter
activity and immune regulation have been identified.
These preliminary findings may provide a useful frame-
work for more in-depth investigations — potentially as
CNS surrogates or biomarkers — of the biological patho-
genesis of a mental health problem. However, we argue
that understanding hidden hypotheses within the EWAS
is an important first step in interpreting the results in
relation to mental health phenotypes.
Conflict of interest statement
Nothing declared.
Acknowledgement
This manuscript was supported by a grant from the Economic and Social
Research Council (ES/R005516/2) to EDB.
References and recommended reading
Papers of particular interest, published within the period of review,
have been highlighted as:
 of special interest
 of outstanding interest
1. Shonkoff JP, Boyce WT, McEwen BS: Neuroscience, molecular
biology, and the childhood roots of health disparities: building
a new framework for health promotion and disease
prevention. J Am Med Assoc 2009, 301:2252-2259 http://dx.doi.
org/10.1001/jama.2009.754.
Current Opinion in Psychology 2019, 27:13–17
2. Barker ED, Walton E, Cecil CAM: Annual research review: DNA
 methylation as a mediator in the association between risk
exposure and child and adolescent psychopathology. J Child
Psychol Psychiatry 2018, 59:303-322 http://dx.doi.org/10.1111/
jcpp.12782.
Very good review on the degree to which DNA methylation links risk
exposure and psychopathology.
3. Klengel T, Mehta D, Anacker C, Rex-Haffner M, Pruessner JC,
Pariante CM, Pace TW, Mercer KB, Mayberg HS, Bradley B et al.:
Allele-specific FKBP5 DNA demethylation mediates gene–
childhood trauma interactions. Nat Neurosci 2013, 16:33.
4. Rijlaarsdam J, Cecil CA, Walton E, Mesirow MS, Relton CL,
Gaunt TR, McArdle W, Barker ED: Prenatal unhealthy diet,
insulin-like growth factor 2 gene (IGF2) methylation, and
attention deficit hyperactivity disorder symptoms in youth
with early-onset conduct problems. J Child Psychol Psychiatry
2017, 58:19-27.
5. Richmond RC, Simpkin AJ, Woodward G, Gaunt TR, Lyttleton O,
 McArdle WL, Ring SM, Smith AD, Timpson NJ, Tilling K: Prenatal
exposure to maternal smoking and offspring DNA methylation
across the lifecourse: findings from the Avon Longitudinal
Study of Parents and Children (ALSPAC). Hum Mol Genet 2015,
24:2201-2217.
Longitudinal study describing the transient, but also partially persistent
effects of maternal smoking on offpsring DNA methylation.
6. Tobi EW, Slieker RC, Luijk R, Dekkers KF, Stein AD, Xu KM,
Slagboom PE, van Zwet EW, Lumey LH, Heijmans BT: DNA
methylation as a mediator of the association between prenatal
adversity and risk factors for metabolic disease in adulthood.
Sci Adv 2018, 4 eaao4364.
7. Feinberg AP: The key role of epigenetics in human disease
prevention and mitigation. N Engl J Med 2018, 378:1323-1334.
8. Rakyan VK, Down TA, Balding DJ, Beck S: Epigenome-wide
 association studies for common human diseases. Nat Rev
Genet 2011, 12:529.
Overview of the strengths and, 2018 overview of the strengths and
challenges of epigenetic research for complex diseases, with recom-
mendations for study design and other considerations.
9. Kitsios GD, Zintzaras E: Genome-wide association studies:
hypothesis-“free” or “engaged”? Transl Res 2009, 154:161-164.
10. McCarthy MI, Abecasis GR, Cardon LR, Goldstein DB, Little J,
Ioannidis JP, Hirschhorn JN: Genome-wide association studies
for complex traits: consensus, uncertainty and challenges. Nat
Rev Genet 2008, 9:356.
11. Gaunt TR, Shihab HA, Hemani G, Min JL, Woodward G,
 Lyttleton O, Zheng J, Duggirala A, McArdle WL, Ho K et al.:
Systematic identification of genetic influences on methylation
across the human life course. Genome Biol 2016, 17:1.
Extremely well-done research studying genetic influences on DNA
methylation.
12. Pidsley R, Zotenko E, Peters TJ, Lawrence MG, Risbridger GP,
 Molloy P, Van Djik S, Muhlhausler B, Stirzaker C, Clark SJ: Critical
evaluation of the Illumina MethylationEPIC BeadChip
microarray for whole-genome DNA methylation profiling.
Genome Biol 2016, 17:208.
Rigorous comparison of the EPIC BeadChip to the HM450 BeadChip and
Whole Genome Sequencing, to evaluate agreement, coverage and
content.
13. Lin D, Chen J, Perrone-Bizzozero N, Bustillo JR, Du Y, Calhoun VD,
Liu J: Characterization of cross-tissue genetic-epigenetic
effects and their patterns in schizophrenia. Genome Med 2018,
10:13.
14. Jones MJ, Moore SR, Kobor MS: Principles and challenges of
applying epigenetic epidemiology to psychology. Annu Rev
Psychol 2018, 69:459-485.
15. Bibikova M, Barnes B, Tsan C, Ho V, Klotzle B, Le JM, Delano D,
Zhang L, Schroth GP, Gunderson KL et al.: High density DNA
methylation array with single CpG site resolution. Genomics
2011, 98:288-295.
16. Bakulski KM, Halladay A, Hu VW, Mill J, Fallin MD: Epigenetic
 research in neuropsychiatric disorders: the “tissue issue”.
Curr Behav Neurosci Rep 2016, 3:264-274.
www.sciencedirect.com

Very good review on the challenges but also potential avenues of using
blood tissue in neuropsychiatric research.
17. Walton E, Hass J, Liu J, Roffman JL, Bernardoni F, Roessner V,
Kirsch M, Schackert G, Calhoun V, Ehrlich S: Correspondence of
DNA methylation between blood and brain tissue and its
application to schizophrenia research. Schizophr Bull 2015.
sbv074.
18. Ladd-Acosta C, Fallin MD: The role of epigenetics in genetic and
environmental epidemiology. Epigenomics 2015, 8:271-283
http://dx.doi.org/10.2217/epi.15.102.
19. O’Bryant SE, Mielke MM, Rissman RA, Lista S, Vanderstichele H,
Zetterberg H, Lewczuk P, Posner H, Hall J, Johnson L: Blood-
based biomarkers in Alzheimer disease: current state of the
science and a novel collaborative paradigm for advancing
from discovery to clinic. Alzheimer’s Dement 2017, 13:45-58.
20. Barker ED, Cecil CAM, Walton E, Meehan AJ: Genetic influences
on childhood disruptive behaviors. In The Wiley Handbook of
Disruptive and Impulse-Control Disorders. Edited by Lochman J,
Matthys W. USA: Wiley-Blackwell; 2017.
21. Breton CV, Marsit CJ, Faustman E, Nadeau K, Goodrich JM,
 Dolinoy DC, Herbstman J, Holland N, LaSalle JM, Schmidt R et al.:
Small-magnitude effect sizes in epigenetic end points are
important in children’s environmental health studies: the
Children’s Environmental Health and Disease Prevention
Research Center’s Epigenetics Working Group. Environ Health
Perspect 2017, 125:511.
Thorough review discussing methodologies in epigenetic research,
robust findings (even of small effect sizes) in longitudinal work, and
implications for the future.
22. Michels KB, Binder AM, Dedeurwaerder S, Epstein CB, Greally JM,
Gut I, Houseman EA, Izzi B, Kelsey KT, Meissner A, Milosavljevic A,
Siegmund KD, Bock C, Irizarry RA: Recommendations for the
design and analysis of epigenome-wide association studies.
Nat Methods 2013, 10:949-955 http://dx.doi.org/10.1038/
nmeth.2632.
23. Hannon E, Lunnon K, Schalkwyk L, Mill J: Interindividual
 methylomic variation across blood, cortex, and cerebellum:
implications for epigenetic studies of neurological and
neuropsychiatric phenotypes. Epigenetics 2015, 10:1024-1032.
This is an important paper, one of the first to show concordance in DNAm
across tissue types, particularly blood and brain.
24. Walton E, Cecil CAM, Suderman M, Liu J, Turner JA, Calhoun VD,
Ehrlich S, Relton CL, Barker ED: Longitudinal epigenetic
predictors of amygdala:hippocampus volume ratio. J Child
Psychol Psychiatry 2017, 58:1341-1350.
25. Hannon E, Weedon M, Bray N, O’Donovan M, Mill J: Pleiotropic
effects of trait-associated genetic variation on DNA
methylation: utility for refining GWAS loci. Am J Hum Genet
2017, 100:954-959.
26. Nusslock R, Miller GE: Early-life adversity and physical and
emotional health across the lifespan: a neuroimmune network
hypothesis. Biol Psychiatry 2016, 80:23-32.
www.sciencedirect.com
Hidden hypotheses Barker, Roberts and Walton 17
27. Felger JC, Li Z, Haroon E, Woolwine BJ, Jung MY, Hu X, Miller AH:
Inflammation is associated with decreased functional
connectivity within corticostriatal reward circuitry in
depression. Mol Psychiatry 2016, 21:1358.
28. Barker ED, Cecil CAM, Walton E, Houtepen LC, O’Connor TG,
 Danese A, Jaffee SR, Jensen SKG, Pariante C, Roberts S,
McArdle W, Gaunt TR, Relton CL: Inflammation-related
epigenetic risk and child and adolescent mental health: a
prospective study from pregnancy to mid-adolescence. Dev
Psychopathol 2018. (in press).
First longitudinal study to employ inflammation-related poly epigenetic
genetic risk scores in relation to pre- and post-natal adversities, neuro-
cognitive function and mental health problems.
29. Ladd-Acosta C: Epigenetic signatures as biomarkers of
exposure. Curr Environ Health Rep 2015, 2:117-125.
30. Liu C, Marioni RE, Hedman AK, Pfeiffer L, Tsai PC, Reynolds LM,
Just AC, Duan Q, Boer CG, Tanaka T et al.: A DNA methylation
biomarker of alcohol consumption. Mol Psychiatry 2016 http://
dx.doi.org/10.1038/mp.2016.192.
31. Hattab M, Clark S, van den Oord E: Overestimation of the
classification accuracy of a biomarker for assessing heavy
alcohol use. Mol Psychiatry 2017 http://dx.doi.org/10.1038/
mp.2017.181.
32. Barker ED: Epigenetics, early adversity and child and
adolescent mental health. Psychopathology 2018, 51:71-75.
33. Felix JF, Joubert BR, Baccarelli AA, Sharp GC, Almqvist C, Annesi-
 Maesano I, Arshad H, Baı̈z N, Bakermans-Kranenburg MJ,
Bakulski KM et al.: Cohort profile: Pregnancy And Childhood
Epigenetics (PACE) Consortium. Int J Epidemiol 2017.
Important example of consortia type efforts.
34. Hannon E, Dempster E, Viana J, Burrage J, Smith AR,
Macdonald R, St Clair D, Mustard C, Breen G, Therman S et al.: An
integrated genetic-epigenetic analysis of schizophrenia:
evidence for co-localization of genetic associations and
differential DNA methylation. Genome Biol 2016, 17:176.
35. Joubert BR, Felix JF, Yousefi P, Bakulski KM, Just AC, Breton C,
Reese SE, Markunas CA, Richmond RC, Xu C-J: DNA
methylation in newborns and maternal smoking in pregnancy:
genome-wide consortium meta-analysis. Am J Hum Genet
2016, 98:680-696.
36. Insel T, Cuthbert B, Garvey M, Heinssen R, Pine DS, Quinn K,
Sanislow C, Wang P: Research domain criteria (RDoC): toward
a new classification framework for research on mental
disorders. Am Psychiatric Assoc 2010, 167:748-751.
37. Cecil CAM, Walton E, Jaffee SR, O’Connor T, Maughan B,
Relton CL, Smith RG, McArdle W, Gaunt TR, Ouellet-Morin I,
Barker ED: Neonatal DNA methylation and early-onset conduct
problems: a genome-wide, prospective study. Dev
Psychopathol 2018, 30:383-397.
38. Fisher HL, Murphy TM, Arseneault L, Caspi A, Moffitt TE, Viana J,
Hannon E, Pidsley R, Burrage J, Dempster EL et al.: Methylomic
analysis of monozygotic twins discordant for childhood
psychotic symptoms. Epigenetics 2015, 10:1014-1023.
Current Opinion in Psychology 2019, 27:13–17